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The Doctor Is In

I’m a little underslept today,” Dr. Francis Collins laughs, sitting in his office in the historic Building 1 of the National Institutes of Health’s sprawling campus in Bethesda, Md., where he presides as the dean of the nation’s health.

They say Collins is indefatigable. He has accomplished so much in his career—from sequencing the human genome to running the largest biomedical research agency in the world—he must not need much sleep.

But on this sunny April afternoon Collins looks as if he could use a nap. Not because of the weightiness of NIH’s mission to prevent disease and prolong human life, but because the previous night he stayed up late to appear on Comedy Central’s talk show The Colbert Report to discuss the BRAIN Initiative, NIH’s audacious project to map the human brain.

It’s possible no public servant is better equipped than Collins to go toe to toe with the bombastic faux-conservative Stephen Colbert. Defying the caricature of a buttoned-up scientist, the 6-foot-4, 63-year-old NIH chief plays guitar in a rock-and-roll band and rides a Harley on weekends. He actually got his start in theater. Home-schooled in rural Virginia, Collins’ father was a drama professor and his mother a playwright. “I was shoved onto the stage by the time I was 5 years old,” he says.

Many officials are explicitly warned not to subject themselves to one of Colbert’s unpredictable interviews, but it was Collins’ fourth appearance on the show.

“He does like medical research,” Collins says of Colbert, whose late father had been a renowned medical doctor and served as associate director for extramural programs at the National Institute of Allergy and Infectious Diseases— one of the 27 institutes and centers Collins oversees. It turns out Colbert, like a majority of Americans—54 percent of whom, according to the nonprofit Research!America, would pay $1 more in taxes each week to support medical research—believes in the work of NIH.

Collins subjects himself to the madness for the same reason every other guest does: the exposure. One of his many objectives as NIH director is public education, to inspire the next generation of scientists. “Any opportunity to do that seems like it’s worth taking some risks,” he says.

The agency, he says, is “the rock upon which American biomedical research excellence and success has been placed.” With a budget of more than $30 billion—83 percent of which funds extramural, or outside, research—NIH supports more than 300,000 scientists at more than 2,500 universities and institutions across all 50 states. Another 10 percent goes to intramural research performed by 6,000 NIH scientists.

But Collins must preserve NIH’s scientific mission after a decade of flat or declining budgets and now sequestration. Because of the perilous budget outlook, many of the young people he is trying to reach might never find employment in the field he hopes will capture their imagination. The current period of political dysfunction has resulted in real hardship for the federal sector and the biomedical research community particularly, according to Collins, who says he never imagined it would get this bad.

Sequestration “was supposed to be this poison pill that was so painful, so destructive that it would never come to pass and yet the Congress swallowed it and we all get poisoned,” he says. “It’s unimaginable that our country, which prides itself on science, technology, innovation and reason, would have allowed this outcome to occur. But here we are.”

Seizing the Moment

The one thing Collins’ mother told him not to do was become a federal employee. The pay isn’t great and the bureaucracy is even worse, she told him. Yet 20 years later, perhaps as a latent form of rebellion, he remains. For 15 years he was head of the National Human Genome Research Institute—the outgrowth of the famous Human Genome Project, which culminated in 2000 at the White House with Collins, alongside President Clinton, announcing the first full mapping of human DNA. After briefly leaving NIH in 2008, Collins was asked to join the Obama transition team, which he says was “sort of a temporary dedication.” That was, until President Obama asked him to become NIH director.

“It clearly didn’t seem like this was going to be an easy time,” says Collins, who assumed the role during the depths of the recession in August 2009. “And it has not been, just in terms of the resources that are continually being whittled away . . . But even in difficult fiscal times there are things that need to happen, and I’m determined to push that agenda as far as I can.”

Despite the air of austerity, Collins’ colleagues say his strength as a communicator and ability to seize the moment have driven significant achievements at NIH—both bureaucratic and scientific.

As some solace to his mother, perhaps it was those formative years on stage that molded him into what his associates call a masterful communicator. Collins is known to bust out his guitar and parody science via song at NIH functions. “It breaks down barriers,” Collins says, noting that by making himself the most vulnerable and silliest person in the room, he can make stuffy scientific forums more human. “If you get everybody to sing together, [the dynamic] is totally different from that point forward.”

Michael Stitzel, a postdoctoral fellow, has worked in Collins’ lab for seven years (yes, he still manages a lab at NIH). “The beauty of his communications style is that it doesn’t matter what level he’s talking to, he can convey his ideas very clearly—he’s a very clear thinker,” says Stitzel. “He can turn [the technical jargon] up or turn it down as need be.”

Princeton University President Shirley Tilghman, a geneticist and former postdoctoral researcher at NIH, says Collins has a remarkable ability to explain complex scientific issues in language anyone can understand. “He doesn’t talk down to his audiences, but what he does is make sure he brings them along,” she says, “And I think that’s a very powerful quality in a leader.”

From the Human Genome Project to NIH, Collins has a record of harnessing complex organizations in a town where getting things done tends to be a foreign concept.

In December 2011, the National Center for Advancing Translational Sciences was established at his behest, something that caused quite a stir. It required the dissolution of the National Center for Research Resources, as well as approval from the scientific community and, most tricky of all, Congress.

There are some 7,000 diseases that affect humans, fewer than 500 of which have any treatment. Translational science seeks to close that gap by turning basic science into treatments that directly improve human health. On average, it takes 13 years before a discovery in a lab produces a new drug or therapy to treat an illness. Along the way, 95 percent of translations fail, and those that succeed can ultimately cost more than $1 billion. The Center for Translational Sciences, still in its infancy and its effectiveness unknown, was designed to be different—bringing together industry, leveraging data and focusing on deliverables to speed the process up and keep the costs down.

“Many people really thought we were moving too fast,” says Collins. “I take that as a badge of courage. If you’re in the government and somebody says you’re moving too fast, maybe that’s not a bad thing.”

His next area of focus was on what Story Landis, director of the National Institute of Neurological Disorders and Stroke, considers the next frontier of scientific exploration: mapping the human brain.

“Once Francis looked at the breadth and depth and wealth of exciting research in the brain sciences, he began to think seriously about a major initiative,” says Landis. The BRAIN Initiative, which stands for brain research through advancing innovative neurotechnologies, is a $100 million public-private partnership between NIH, the Defense Advanced Research Projects Agency, the National Science Foundation and several nonprofits to unlock the secrets of the human brain. “Making progress on the burden of neurological disorders, if you think of Alzheimer’s, Parkinson’s disease, schizophrenia and bipolar disorders, is going to require a much better understanding than we currently have,” says Landis.

President Obama previewed the BRAIN Initiative, which is styled after the Human Genome Project, in his 2013 State of the Union address, noting its scientific and economic importance. “Every dollar we invested to map the human genome returned $140 to our economy—every dollar,” Obama said.

Biomedical research returns about $2 in economic activity for every $1 in taxpayer investment, Collins says, which is why so many in the field are bewildered by the budget situation they are in.

A Bad Year

The five years between 1998 and 2003 is known in the scientific community as “the doubling”—a period in which biomedical research, with bipartisan support, was made a top national priority and NIH’s budget spiked from $13.6 billion to $27.1 billion. Budgets have been flat or declining ever since, with inflation eating away at NIH’s real purchasing power by 22 percent over the past 10 years.

For a scientist seeking funding for a great idea, the chances have decreased. In fact, they’ve been cut by almost half. In 2000, the chance of an investigator’s grant application being approved was on average 32 percent; in 2012, the odds were 18 percent. Depending on which center a researcher applies to, the approval rate can be as low as 10 percent.

“It’s a bad year to have a good idea,” says Mary Wolley, president of Research!America, which is pushing to make health research a national priority.

As a result of sequestration, the life sciences are projected to lose 20,500 jobs this year. NIH’s fiscal 2013 budget fell by $1.71 billion, or 5.5 percent, compared with fiscal 2012. “That’s the size of my whole budget for a year,” says Landis, referring to the $1.6 billion budget for the Institute of Neurological Disorders and Stroke. If sequestration is not reversed, NIH could lose $19 billion over the next 10 years.

A recent Research!America poll showed a majority of Americans, 83 percent, believe that investing in medical innovation has a role in creating jobs and fueling the economy. In addition, an ABC News/Washington Post poll published in May reported 56 percent of Americans disapprove of the sequester. That sentiment is echoed on both sides of the aisle, particularly when it comes to cutting NIH funding.

Sen. Tom Coburn, R-Okla., is no fan of government spending and was recently named the 12th most conservative senator by National Journal, a sister publication of Government Executive. But when it comes to cutting medical research, he is firmly against it. “We shouldn’t be cutting back on that at all,” says Coburn, who is also a doctor. “We’re almost at a new frontier in terms of medical research and scientific discovery . . . We have so much waste in other areas of the government that we shouldn’t have to cut NIH at all—as matter of fact, we should be doubling it again.”

Accounting for the sequester, Collins recently told Congress that NIH intends to award 700 fewer grants, compared with 2012, any number of which he contends could have led to a significant discovery.

“The thing about funding research is that it’s not like a light switch,” says Chris Hansen, president of the American Cancer Society’s Cancer Action Network. “You can’t just turn it on and off. When you turn the switch off you’re not only losing the benefit of the research that would go on now, you’re losing the benefit of the research that led up to that point.”

Workforce Woes

In the science world, telling someone you’re pursuing a doctoral degree in biomedical research is like saying you’re majoring in theater—you might make it, but the odds aren’t good.

“There are times I think I’m crazy for continuing in this with shrinking budgets and much higher competition,” says Stitzel, 35, the postdoctoral fellow in Collins’ lab who is looking for a faculty position. “[Young scientists] are all writing grants, we’re trying to get funding, we’re thinking of starting labs—but it’s so discouraging.”

Scientists seeking NIH funding spend more time writing grants than doing science, says Collins. With success rates for new research grants as low as one in 10, many researchers who received the green light are now seeing their projects frozen due to sequestration. And those who succeed in getting funding likely have a saint’s patience. The average age of a researcher winning his first independent NIH grant last year was 44, up from 36 in 1980.

As countries like Germany, Singapore, India and China increase their investments in biomedical research, the United States stands out with its spending cuts. Many scientists consider leaving the country or moving to industry, where the pay and occupational stability are much higher, says Tilghman, who co-led an NIH-commissioned task force to study the biomedical workforce. Once they leave the field they rarely come back.

The starting salary for NIH-funded postdoctorates is about $39,000 a year. After spending seven or more years in postdoctoral training, those who get tenured positions as new associate professors of biomedical research can expect to make $68,000. In industry, starting pay for Ph.D.s can be closer to $80,000 to $100,000 a year.

In the private sector, the focus is short-term and profit-driven research. It can take years for government-funded basic research to pay off. It’s a process of trial and error that is the backbone of scientific progress, and something industry shareholders have little patience for, according to Collins.

He and others worry the already difficult environment, made worse by sequestration, will result in a lost generation of scientists—an impact that won’t be felt for decades.

“It is hard to prove a negative,” says Collins. “We will not know what grant that was going to lead to the next breakthrough in cancer research didn’t quite make the cut. We will not know what brilliant scientists, who were going to win a Nobel Prize, basically gave up because of the failure to get support from the current system and decided to do something else or move to another country. We won’t know. That is the sad tale that is wrapped up in all of this.”

Spreading Hope

If the success of NIH leadership were judged in dollars and cents, Collins would not fare well. “I certainly can’t claim that I’ve been able to turn the tide here in terms of support for research,” he says. “Under my particular directorship the support for NIH has sunk to the lowest level, proportionally, than it’s been in years. That’s not something to feel very proud about.”

But few in the field would categorize Collins’ tenure that way.

“I would be the first person to be critical, honestly,” says Hansen, who’s American Cancer Society is the largest nongovernmental funder of cancer research in the United States. “I think he’s doing the best job anybody can humanly do under these circumstances. Partly because of Dr. Collins, people understand how stupid and mindless the [sequester is].”

Sen. Tom Harkin, D-Iowa, chairman of the Senate Committee on Health, Education, Labor and Pensions, says Collins is masterful at explaining the promise of biomedical research. “I’ve never ended a conversation with him without feeling smarter and more hopeful for the future,” he says.

Collins seeks to spread that hope—to share the stories of progress at NIH—from Congress to Colbert to the families affected by diseases that he and his team strive to defeat. Challenges and all, Collins’ passion for the job is reflected in his vision for the future.

“This is just an amazing time in terms of science,” he says. “The ability to unravel mysteries that have stumped us for all of human history—and here we have the talented people working on this and the tools to do this. How could you not be inspired by being able to stand at the helm of this ship and try and steer it in the right direction?”

Notable NIH Research Programs

BRAIN Initiative Announced by President Obama in April, the BRAIN Initiative is a $100 million effort to develop brain-mapping technologies that can observe neural activity in real time, helping treat diseases including Alzheimer’s and Parkinson’s.

The Cancer Genome Atlas (tcga)TCGA has sequenced the DNA of more than 20 types of cancer. By observing molecular changes in cancer cells,scientists are identifying commonalities between cancers and developing treatments that cater to patients’ unique genetic profiles.

Universal Flu Vaccine Recent advances in understanding proteins common in all strains of flu have put NIH researchers within striking distance of a universal flu vaccine—one that would eliminate the need for yearly flu shots, saving lives and reducing costs.

Human Microbiome (HMP) Fungus, bacteria and other microbes live all over our bodies, outnumbering human cells 10 to 1. HMP studies these microbial communities to better understand their connection to development, immunity and nutrition.

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